Sensitization of T-cell receptor-αβ⁺ T cells recovered from long-term T-cell receptor downmodulation

Although the survival of fully allogeneic skin grafts was prominently prolonged by adult thymectomy in anti-T-cell receptor-αβ monoclonal antibody (TCR-αβ mAb)-treated mice compared with that of non-adult thymectomized (ATX) mice, the skin allografts were eventually rejected. In the anti-TCR-αβ mAb-treated ATX mice, as shown in the present study, most of TCR-αβ⁺ cells were promptly activated on day 2 and then rapidly disappeared by day 7, but some TCR-αβ Thy-1⁺ cells remained at that time. These TCR-αβ⁺ Thy-1⁺ cells which have downmodulated their TCR-αβ expression may be refractory to depiction events by the mAb treatment. Although these downmodulated T cells re-expressed their TCR-αβ on day 50, they could not respond to stimuli via TCR such as TCR cross-linking or alloantigens. However, they recovered the reactivity to donor antigens on day 85. These results indicate that the downmodulated T cells by anti-TCR-αβ mAb treatment are long-lived and re-express their TCR-αβ at a late stage to be sensitized to donor antigen, which suggests that additional regimens may be required to get permanent, or very long-term, graft acceptance.